Observation of Chronic Graft-Versus-Host Disease Mouse Model Cornea with In Vivo Confocal Microscopy

Abstract

Graft-versus-host disease (GVHD) is a major complication after hematopoietic stem cell transplantation (HSCT), and ocular GVHD can cause severe dry eye disease that can lead to visual impairment. Epithelial damage, vascular invasion, corneal fibrosis, and corneal perforation may occur in severe cases. It is generally accepted that inflammatory cells such as dendritic cells and T cells contribute to this pathological condition. However, it is still unknown what pathological condition occurs on the ocular surface after HSCT, and when. We therefore observed the dynamics of inflammatory cells in the cornea of chronic GVHD (cGVHD) model mice from 1 to 4 weeks after bone marrow transplantation (BMT) by in vivo confocal microscopy (IVCM) and considered the relationship with the pathophysiology of ocular GVHD (tear volume, corneal epithelial damage). In the allogeneic group, neovascularization occurred in all eyes at 1 week after BMT, although almost all vessels disappeared at 2 weeks after BMT. In addition, we revealed that infiltration of globular cells, and tortuosity and branching of nerves in the cornea occurred in both cGVHD mice and human cGVHD patients. Thus, we consider that cGVHD mouse model study by IVCM reproduces the state of ocular GVHD and may contribute to elucidating the pathological mechanism for ocular GVHD.

Keywords

• hematopoietic stem cell transplantation
• bone marrow transplantation
• graft-versus-host disease
• dry eye disease
• in vivo confocal microscopy